Upregulation of Aquaporin-3 Is Involved in Keratinocyte Proliferation and Epidermal Hyperplasia

Aquaporin-3 (AQP3) is a water/glycerol-transporting protein expressed in keratinocytes of the epidermis. We previously showed that AQP3-mediated transport of water and glycerol is involved in keratinocyte migration and proliferation, respectively. However, the involvement of AQP3 in epidermal hyperplasia in skin diseases, such as atopic dermatitis (AD), is unknown. In this study, we found significantly increased AQP3 transcript and protein expression in the epidermis of human AD lesions. The upregulation of AQP3 expression in human keratinocytes by transfection with human AQP3 DNA plasmid was associated with increased cellular glycerol and ATP, as well as increased cell proliferation. Among several cytokines and chemokines produced in the skin, CCL17, which is highly expressed in AD, was found to be a strong inducer of AQP3 expression and enhanced keratinocyte proliferation. In mouse AD models, AQP3 was strongly overexpressed in the epidermis in wild-type mice. Epidermal hyperplasia was reduced in AQP3-deficient mice, with a decreased number of proliferating keratinocytes. These results suggest the involvement of AQP3 in epidermal hyperplasia by a mechanism involving upregulated AQP3 expression and consequent enhancement of keratinocyte proliferation

Aquaporin-3の発現増加は表皮角化細胞の増殖および表皮肥厚に関与する

京都大学0048新制・課程博士博士(医学)甲第16697号医博第3645号新制||医||991(附属図書館)29372京都大学大学院医学研究科医学専攻(主査)教授 鈴木 茂彦, 教授 三森 経世, 教授 長澤 丘司学位規則第4条第1項該当Doctor of Medical ScienceKyoto UniversityDA

Generalized papules in a patient with acute meloid lukemia quiz case

REPORT OF A CASE A 58-year-old Japanese man, who had been followed up and received blood transfusions regularly for myelodysplastic syndrome (refractory anemia with an excess of blast cells) for 1 year, developed acute myeloid leukemia. He had pancytopenia, with a white blood cell (WBC) count of 800 cells/\ub5L (to convert to x 109/L, multiply by 0.001), neutropenia (7.0 % of WBCs), and increased circulating blast cell count (58% of WBCs). He had received fluconazole as antifungal prophylaxis. He commenced chemotherapy via a central venous catheter. On day 11, he had a high fever, and a blood culture was taken. On day 13, he presented with asymptomatic papules on the upper limbs (Figure 1), which spread over the trunk, face, and lower limbs on the nextday. These papules were 5 to 10 mm in diameter and some appeared purpuric. He . . MICROSCOPIC FINDINGS AND CLINICAL COURSE The skin biopsy specimen showed microabscesslike clusters of eosinophilic small round bodies within the blood vessels of the upper dermis. Periodic acid\u96Shiff and Grocott stains showed that these small bodies were positive for microorganisms. There were no microorganisms in the corneal layer. Parakeratosis, subtle dyskeratosis in the epidermis, and vacuolar change in the basal layer were also seen. A blood culture yielded Candida krusei. Based on these findings, we diagnosed these eruptions as fungal emboli due to systemic C krusei infection. After the diagnosis, his central venous catheter was removed and his antifungal drugs were changed to voriconazole and micafungin because C krusei is resistant to fluconazole. The eruptions improved, but he had resistant fever. Chest and abdominal computed tomography detected multiple low-density areas in the lungs and liver that were clinically due to systemic C krusei infection. Because C krusei in our case was sensitive to amphotericin B . .

Reduction of Skin pH during Treatment for Palmoplantar Hyperhidrosis: A Conjecture on the Role of pH-Regulated Water Channel, i.e. Aquaporin

Primary palmoplantar hyperhidrosis (PPH) is a disorder that involves excessive sweating on the palms and soles. Although the pathophysiology of PPH remains unknown, some treatments, including topical aluminum chloride (AC) and tap water iontophoresis (TWI), are effective at suppressing the perspiration. Herein, we report the kinetics of the skin pH of two cases of PPH treated with AC and TWI. We found that the skin pH decreased in accordance with the reduction in sweating. This finding indicates that the reduction in sweating may be attributed to the reduction of skin pH in AC and TWI. Whether or not the pH-regulated function of aquaporin can explain this finding remains unknown

Normal Immunostaining Pattern for Aquaporin-5 in the Lesions of Palmoplantar Hyperhidrosis

Aquaporin-5 (AQP-5) is a water-transporting protein expressed in mammal sweat glands. It has been reported that the expression of AQP-5 is involved in sweating of mice, rats, and horses. However, the physiological function of human AQP-5 is still uncertain. In this report, we examined the expression pattern of AQP-5 in the skin lesions of palmoplantar hyperhidrosis in patients with Nagashima-type palmoplantar hyperkeratosis (PPK). We found that there was no significant difference in AQP-5 expression in the palmoplantar skin of healthy subjects and patients with palmoplantar hyperhidrosis. Our findings suggest that a mechanism other than AQP-5 may be involved in the pathogenesis of hyperhidrosis in PPK

Evaluation of Basophil Infiltration into the Skin Lesions of Tick Bites

Recently, it has been described that basophils play an essential role in antibody-mediated acquired immunity against ticks in mice. However, it is still unknown whether basophil infiltration has any significance in the infestation with ticks in humans. In this report, we have evaluated the infiltration of basophils into human skin lesions of tick bites

Analysis of aquaporin 9 expression in human epidermis and cultured keratinocytes

Aquaporin 9 (AQP9) is a member of the aquaglyceroporin family that transports glycerol, urea and other small solutes as well as water. Compared to the expression and function in epidermal keratinocytes of AQP3, another aquaglyceroporin, our knowledge of epidermal AQP9 remains elusive. In this study, we investigated the expression of AQP9 in the human epidermis and cultured keratinocytes. Immunofluorescence studies revealed that AQP9 expression is highly restricted to the stratum granulosum of the human epidermis, where occludin is also expressed at the tight junctions. Interestingly, the AQP3 staining decreased sharply below the cell layers in which AQP9 is expressed. In cultured normal human epidermal keratinocytes (NHEK), knock-down of AQP9 expression in the differentiated cells induced by RNA interference reduced glycerol uptake, which was not as pronounced as was the case with AQP3 knock-down cells. In contrast, similar reduction of urea uptake was detected in AQP9 and AQP3 knock-down cells. These findings suggested that AQP9 expression in NHEK facilitates at least the transport of glycerol and urea. Finally, we analyzed the effect of retinoic acid (RA), a potent stimulator of keratinocyte proliferation, on AQP3 and AQP9 mRNA expression in differentiated NHEK. Stimulation with RA at 1 μM for 24 h augmented AQP3 expression and down-regulated AQP9 expression. Collectively, these results indicate that AQP9 expression in epidermal keratinocytes is regulated in a different manner from that of AQP3